MicroRNA-345-5p acts as an anti-inflammatory regulator in experimental allergic rhinitis via the TLR4/NF-κB pathway

TLR4型 基因沉默 鼻粘膜 卵清蛋白 小RNA 炎症 NF-κB 细胞凋亡 信号转导 免疫学 Toll样受体 癌症研究 化学 生物 细胞生物学 先天免疫系统 免疫系统 生物化学 基因
作者
Jie Liu,Yan Jiang,Min Seok Han,Liwei Jiang,Dapeng Liang,Shenling Li,Zhengji Xu,Lin Wang,Na Li
出处
期刊:International Immunopharmacology [Elsevier]
卷期号:86: 106522-106522 被引量:17
标识
DOI:10.1016/j.intimp.2020.106522
摘要

Allergic rhinitis (AR) is a common chronic condition characterized by inflammation of the nasal mucosa. The correlation of microRNAs (miRNAs) in AR has been highlighted particularly due to their roles in regulating inflammatory responses. The aim of this study was to explore the anti-inflammatory mechanism by which miR-345-5p regulates the toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway in mice with AR. Initially, the putative miR-345-5p binding sites on the 3′untranslated region of TLR4 was predicted and verified. AR models were established using ovalbumin, after which the functional role of miR-345-5p in AR was determined using gain- and loss-of-function approaches. We found that miR-345-5p was poorly expressed in nasal mucosal tissues of mice with AR. Meanwhile, TLR4 expression and the TLR4/NF-κB pathway were identified to be promoted, which were then suppressed in the presence of overexpressed miR-345-5p. In addition, nasal epithelial cell apoptosis and fibrosis were inhibited in response to miR-345-5p overexpression and TLR4 silencing. Furthermore, miR-345-5p overexpression and TLR4 silencing were observed to decrease Th2 cells, expression of pro-inflammatory factors, but to increase Th1 cells and expression of anti-inflammatory factors. This study demonstrates an important role of miR-345-5p in alleviating the inflammatory response in mice with AR by inhibiting the TLR4/NF-κB pathway. Therefore, a better understanding of this process may aid in the development of novel therapeutic agents of AR.
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